Studies

USA (Arizona)
Centruroides exilicauda (= C. sculpturatus)

Curry et al. 1983–84: 673 scorpion stings. Identification: identification of scorpions brought in by the victims; indirect criteria, e.g. clinical picture consistent with signs and symptoms of C. exilicauda stings; grade 1 envenoming (see below) may be caused by other scorpions than C. exilicauda in Arizona, but grades 2, 3 and 4 (see below) only by C. exilicauda.

Classification:

• Grade 1: local pain and/or local paraesthesias.
• Grade 2: grade 1 plus pain and/or paraesthesias distant from the site of the sting.
• Grade 3: either neuromuscular dysfunction of the cranial nerves or neuromuscular dysfunction of the skeletal muscles.

1. Cranial nerve dysfunction: blurred vision, "wandering" eye movements, hypersalivation, difficulty in swallowing, tongue fasciculations, problems with the upper respiratory tract, slurred speech. 
2. Neuromuscular dysfunction of the skeletal muscles: jerking of the skeletal muscles, restlessness, involuntary movements that may be mistaken for cerebral seizures.

• Grade 4: both neuromuscular dysfunction of the cranial nerves and neuromuscular dysfunction of the skeletal muscles (there were cases of serious envenoming in all age groups, but it was more common in children <10 years old).

Gateau et al. 1992: 151 scorpion stings. Identification: stings were attributed to C. exilicauda.
Likes et al. 1984: 438 scorpion stings. Identification: stings were attributed to C. exilicauda.
Rimsza et al. 1980: 24 scorpion stings (80% of stings in children <10 years old, 40% in children <4 years old). Identification: stings were attributed to C. exilicauda.

Mexico (Leon, Guanajuato State)
Dehesa-Davila 1989: 38,068 scorpion stings. Identification: the majority of the stings were attributed to C. infamatus infamatus; criteria: epidemiological.

Case reports

USA
Centruroides exilicauda
Rachesky et al. 1984: 2 C. exilicauda stings in children <12 months. Identification: confirmed in one case.

Centruroides sp.

Trestrail 1981: 3 Centruroides sp. stings. Identification: C. hentzi 2/3 and C. exilicauda 1/3; in all 3 cases the scorpion was available for identification; the stings occurred outside the natural areas of distribution of these scorpions.

Signs & symptoms

Autopharmacological effects

Experimental and clinical observations suggest that the major systemic effects of envenoming are caused by endogenous catecholamines and acetylcholine, which are released in response to scorpion venom. As these are transmitters in the sympathetic, parasympathetic and somatic nervous systems, the resulting clinical symptoms of envenoming are dealt with in the section "Neurological effects".

However, scorpion venoms are also believed to lead to other indirect effects that are caused by the release of autopharmacologically active substances (such as kinins, prostaglandins and slow-reacting substances). The pathophysiological effects of these substances overlap to a great extent. This makes it difficult to be certain about aetiology. In particular with regard to pulmonary oedema, there has been discussion concerning the effects of mediators on vascular permeability, which might constitute a non-cardiac component of the pulmonary oedema. Peripheral blood pressure regulation is also responsive to a variety of different mediators that might be released.

Local effects

Centruroides exilicauda

Grade 1: local pain and/or local paraesthesias 515/673. Onset: immediately after the sting;  duration: <24 h in all children <10 years; >24 h in 93 of 382 patients >10 years, maximum duration probably 2 weeks (Curry et al. 1983–84).
Local pain: 29/151 (Gateau et al. 1992).
Local pain: 11/24 (Rimsza et al. 1980).

Centruroides hentzi

Transient local pain and oedema, no systemic signs of envenoming, 2/2 (Trestrail 1981).

Scorpion stings in Mexico, Leon, Guanajuato State (the majority of the stings were attributed to C. infamatus infamatus on the basis of epidemiological criteria). Local signs of envenoming (burning local pain, local erythema, oedema and pruritus) 17,775/38,086 (Dehesa-Davila 1989).

Neurological effects (autonomic and somatic nervous systems)

The venom of Centruroides sp., in contrast to the venoms of Mesobuthus (= Hottentotta) sp., Leiurus sp. and Tityus sp., appears to cause primarily neuromuscular effects. Nonetheless, transient early cholinergic effects, such as vomiting, profuse sweating, hypersalivation and arterial hypotension, and later occurring, longer-lasting adrenergic effects, such as arterial hypertension and tachycardia, have also been described. In contrast to envenoming with Mesobuthus sp., Leiurus sp. and Tityus sp., pulmonary oedema and myocardial damage are not dominant characteristics of severe Centruroides sp. envenoming. The same is true for priapism (Curry et al. 1983–84, Likes et al. 1984).

Centruroides exilicauda

Grade 2: grade 1 plus pain and/or paraesthesias distant from the site of the sting, 61/673. Onset: within <5 h after the sting; duration: <24 h in all children <10 years; >24 h in 93 of 382 patients >10 years, maximum duration probably 2 weeks (Curry et al. 1983–84).

Grade 3: neuromuscular dysfunction of the cranial nerves or neuromuscular dysfunction of the skeletal muscles, 32/673. Onset within <5 h after the sting (Curry et al. 1983–84).

Grade 4: neuromuscular dysfunction of the cranial nerves and neuromuscular dysfunction of the skeletal muscles, 20/673. Onset within <5 h after the sting; this grade of sting is life-threatening due to hypersalivation and mucous secretion in the respiratory tract and dysfunction of the cranial nerves that control the patency of the upper airways (Curry et al. 1983–84).

Restlessness 89/151, nystagmus 87/151, paraesthesias 59/151, hypersalivation 53/151, fasciculations 52/151, blurred vision 50/151, difficulty in swallowing 50/151, slurred speech 25/151 (Gateau et al. 1992).

Tachycardia 22/24, restlessness 9/24, rolling eye movements 8/24, arterial hypertension 8/24, tachypnoea 6/24, laboured respiration 6/24, blurred vision 4/24, slurred speech 4/24, stridor 4/24, vomiting 2/24, bronchospasm 2/24, dysphagia 1/24 (Rimsza et al. 1980).
Opisthotonus 2/2 (both <12 months) (Rachesky et al. 1984).

Scorpion stings in Mexico, Leon, Guanajuato State. The majority of the stings were attributed to C. infamatus infamatus on the basis of epidemiological criteria. Systemic signs of envenoming: nausea, vomiting, distended abdomen, confusional state, hyperexcitability, cerebral seizures, ataxia, nystagmus, hyperthermia, sweating, hypersalivation and hyperlacrimation, increased nasal and bronchial secretion, dysphagia, tachypnoea, dyspnoea, pulmonary oedema, arterial hypertension or hypotension, tachycardia or bradycardia, cardiac insufficiency, 20,293/38,068 (Dehesa-Davila 1989).

Muscular effects

Direct muscular effects have been discussed (Curry et al. 1983–84).

Cardiac effects

The pathogenesis of myocardial damage has not been conclusively clarified. The myocardial and vascular effects of endogenous catecholamines released by scorpion venom are one component, and probably the principal one (see above: "Neurological effects"). However, direct toxic effects of the scorpion venom are also conceivable.

According to the available descriptions of patients suffering from a Centruroides sp. sting, myocardial damage appears to play at most a very minor role or none at all. This is in contrast to envenoming with Mesobuthus sp., Leiurus sp. and Tityus sp. (Curry et al. 1983–84, Likes et al. 1984).

Case fatality rate

0/38,068 scorpion stings in Mexico (Leon, Guanajuato State). The majority of the stings were attributed to C. infamatus infamatus on the basis of epidemiological criteria. All patients with 2 or more signs of systemic envenoming were treated with antivenom (Dehesa-Davila 1989).

Laboratory and physical investigations

1. ECG
No data.

2. Echocardiography and scintigraphy ("radionuclide angiography")
No data.

3. CK-MB, CPK, SGOT
No data

4. Catecholamine metabolites in urine
No data.

5. Blood sugar
Increased (317 mg/dl) (Rachesky et al. 1984).

6. Serum amylase
Neither sensitive nor specific as a parameter for acute pancreatitis. No data.

7. Plasma immunoreactive cationic trypsin
A very sensitive and specific parameter for acute pancreatitis. No data.

8. Leucocytes
Leucocytosis (31,600/mm³) (Rachesky et al. 1984).

Treatment (symptomatic)

1. Local pain

Local cooling with ice and analgesics (Curry et al. 1983–84).

 

2. Monitoring of patients with systemic envenoming
All patients with systemic envenoming are carefully monitored with regard to vital signs, if possible in an intensive care unit. It must be ensured that highly agitated patients do not harm themselves (Curry et al. 1983–84).

3. Patients with respiratory failure
Endotracheal intubation and artificial respiration (Curry et al. 1983–84).

4. Symptomatic medications

In the USA, corticosteroids, antihistamines and calcium used to be administered for scorpion stings, but with no rational basis. Today they are no longer used.

Barbiturates and benzodiazepines are used to control the excessive neuromuscular activity. High-dose long-acting sedative-hypnotic therapy induced adverse reactions, including respiratory depression requiring artificial respiration, respiratory arrest and hypoxic brain injury (Curry et al. 1983–84, Rimsza et al. 1980, Berg and Taratino 1991, Gibly et al. 1999).

With the exception of midazolam, a short acting benzodiazepine with anxeolytic and amnestic properties, all other forms of sedative-hypnotic drugs are no longer in use. On the basis of data from a retrospective study it was concluded that continuous intravenous midazolam infusion can be a safe, and readily available treatment option for patients with grade III and grade IV Centruroides exilicauda (= C. sculpturatus) envenoming. Adequate airway, breathing, and circulation have to be assured: continuous cardiac monitoring, pulse oximetry with continuous clinical bedside monitoring of the patient's respiratory status and clinical response to therapy, effective (Gibly et al. 1999). Midazolam was given to patients of the participnats of the randomized, double-blind clinical trial comparing "Anascorp" with placebo with the dose of midazolam administered as a secondary endpoint (Boyer et al. 2009).

Treatment (specific)

Antivenoms

 

1. Scorpion antivenom (Iatric Laboratories, Phoenix, Arizona; immunised goats)

Curry et al. 1983–84: 1–2 vials i.v. over a period of 15–30 min.

Gateau et al. 1992: 151 patients treated with antivenom (see above “Signs and symptoms”); 1 vial  i.v. 103/151, 2 vials i.v. 36/151, 3 vials i.v. 5/151, 4 vials i.v. 1/151. Average time between sting and antivenom administration 139 min (5 min–10 h).

LoVecchio et al. 1999: 116 patients with grade III or IV envenoming receiving antivenom.

Efficacy: Reversal of severe neurological signs and symptoms within minutes. Complete disappearance, also of more minor clinical neurological signs, within <1.5 h. In contrast, children who were not treated with antivenom had grade 3 symptoms (see above for definition) for up to 9 h and adults for up to 12 h. Similar differences are cited for patients with grade 4 symptoms (Curry et al. 1983–84).
Improvement of symptoms after one vial of antivenom 103/151, in all other patients there was improvement after further doses of antivenom. The average time between antivenom administration and improvement of symptoms was 39 min (Gateau et al. 1992).
Improvement of severe neurological symptoms and vital functions within 1 h (Rachesky et al. 1984).

Adverse reactions

Extremely low rate of adverse reactions. Of 30 patients treated with scorpion antivenom, none had a reaction to the antivenom (Curry et al. 1983–84). Immediate hypersensitivity reactions 16/151, none serious (Gateau et al. 1992), 4/116 (LoVecchio et al. 1999), serum sickness not reported (Gateau et al. 1992), 60/171 with 21-day follow-up (LoVecchio et al. 1999). 

 

 

2. Anascorp, Centruroides (scorpion) immune F(ab')₂ intravenous (equine), Instituto Bioclon (C. limpidus limpidus, C. l. tecomanus, C. noxius, C. suffusus suffusus)

Boyer et al 2009: Randomized, double-blind clinical trial comparing "Anascorp" with placebo. N=15, age 6 months to 18 years, clinically significant signs of scorpion envenoming (characteristic neuromotor agitation with wild flailing of extremities, oculomotor manifestations, and respiratory compromise), admitted to ICU within 5h after being stung. Primary endpoint: resolution of clinical syndrome within 4 hours after andministration of antivenom / placebo. Secondary endpoints: total dose of concomitant midazolam for sedation and quantitative plasma venom levels, before and after treatment.

Efficacy: Primarory endpoint reached by 8/8 of the antivenom and 1/7 of the placebo recipients (p=0.001). Secondary endpoints: more midazolam administered to placebo recipients than to antivenom recipients (p=0.01) and plasma venom undetectable in 8/8 of the antivenom and 1/7 in the placebo recipients 1 after treatmen (n=0.001).

Adverse reactions: Anaphylaxis ot serum sickness: none.

 

3."Alacramyn" antiscorpion serum, Zapata Labs, Mexico City, Mexico
^{Now: Laboratories Bioclon S. A. (previously MYN, Zapata and Grupo Pharma), Calzada de Tlaplan 4687, C.P. 14050 Mexico D.F., Mexico (Dehesa-Davila and Possani 1994).}

Dehesa-Davila 1989: 38,068 scorpion stings in Mexico (Leon, Guanajuato State). The majority of the stings were attributed to Centruroides infamatus infamatus on the basis of epidemiological criteria (see above “Signs and symptoms”). All patients with 2 or more signs of systemic envenoming (20,293/38,068) were treated with antivenom [in general 1 vial with chlorpheniramine (antihistamine) in the same syringe]. Most patients were treated within 10–30 min after the sting. No patients died.

Efficacy: Complete reversal of symptoms within 2–3 h after antivenom administration (Dehesa-Davila 1989).

Adverse reactions: No antivenom reactions were observed with a total of 20,293 antivenom doses (?!). This can be explained in part by the simultaneous administration of an antihistamine (Dehesa-Davila 1989).

 

 

Assessment of the value of antivenom in the treatment of scorpion stings

Among critically ill children with neurotoxic effects of Centruroides envenoming, i.v. administration of scorpion-specific F(ab')₂ antivenom resolved the syndrome within 4 hours, reduced the need for concomitant sedation with midazolam, and reduced the levels of circulating anbound venom. Generalizability of these results is limited by the age group studied and the potential for geograhic variation in scorpion venom (Boyer et al 2009).

 

On the basis of good clinical experience, several authors recommend the use of antivenom for severe C. exilicauda envenoming (Curry et al. 1983–84, Gateau et al. 1992). Antivenom treatment should be considered in particular in children <10 years old and if >3–4 symptoms are present. In most cases 1 vial of antivenom is sufficient (Gateau et al. 1992).
The cross-reactivity of 4 antivenoms:

• Scorpion antivenom (goat) (Anivenin Production Laboratory at Arizona State University, Tempe, Arizona, USA),
• Antialacron-DL (Zapata Laboratory, Mexico),
• Suero Antialacron Equino (Gerencia General de Biologicos y Reactivos, Mexico) and
• Alacramyn (Laboratory "Myn" S.A., Mexico)

to C. exilicauda and C. elegans appears to be good. The in vitro reaction of the North American goat antivenom was, however, better than that of the Mexican horse antivenoms (Bloom et al. 1992).
In Mexico the efficacy of antivenom is rated highly (Dehesa-Davila  1989, Dehesa-Davila and Possani 1994).